GABA(B) receptor antagonists elevate both mRNA and protein levels of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) but not neurotrophin-3 (NT-3) in brain and spinal cord of rats

In this study we show that single, physiologically-active and non-convulsive doses of the three GABA(B) receptor antagonists CGP 36742, CGP 56433A and CGP 56999A increase NGF and BDNF mRNA levels by 200-400% and protein levels by 200-250% in rat neocortex, hippocampus as well as spinal cord. In all areas examined the increase in NGF protein preceded that of BDNF. Peak levels of both neurotrophins are transient and occur between 24 and 72 h, depending on the region. In contrast, NT-3 protein concentrations in the neocortex and hippocampus were decreased significantly to 50% of control values within 48-96 h. The decrease in the spinal cord was less than 30% and did not reach significant levels. These data clearly demonstrate that GABA(B) receptor antagonists induce a specific neurotrophin expression in the central nervous system at physiologically relevant doses, as opposed to the extreme conditions of seizure paradigms. The results are in line with the concept that neuronal neurotrophin synthesis and release in brain are controlled by afferent nerve activity. GABA(B) receptor antagonists could therefore be a valuable new approach to selectively increase endogenous neurotrophin levels in the central nervous system.     

Pharmacokinetic study of valproic acid in a neonate

Valproic acid was administered to a neonate (gestational age of 39 weeks) at 24 days post partum in an initial single dose of 7.5 mg/kg. Multiple serum samples were collected for 24 hours post dose. Valproic acid was continued and the study was repeated in the same child at 6 months of age at which time the dose had been increased to 13.5 mg/kg (27 mg/kg/day). Serum samples were collected for 12 hours post dose in this second study. A one-compartment model was assumed for calculation of the relevant pharmacokinetic parameters. The half-life (t 1/2) at 24 days of age was 17.2 hours, clearance (Cl) 0.18 ml/min/kg, and volume of distribution (Vd) 0.28 liter/kg. This t 1/2 was less than reported values in neonates younger than 10 days but longer than the average t 1/2 in adults. At 6 months of age, clearance had increased to 0.53 ml/min/kg, t 1/2 had decreased to 7.5 hours, while Vd was relatively unchanged (0.34 liter/kg). Factors possibly causing these changes include hepatic enzyme maturation and concomitant administration of anticonvulsant drugs.     

Nutritive value of N-acetyl-L-tryptophan in man.

The nutritive value of N-acetyl-L-tryptophan was investigated by loading tests with deuterated L-tryptophan and deuterated N-acetyl-L-tryptophan in three healthy adults, and by a 7 day-long feeding experiment with deuterated N-acetyl-L-tryptophan in one healthy adult. After loading with deuterated N-acetyl-L-tryptophan, serum levels of deuterated tryptophan and kynurenine were only about 10%, and the amounts of deuterated 5-hydroxyindole-3-acetic acid excreted in 24 h approximately 30% of those found after deuterated tryptophan loading. During the feeding experiment with deuterated N-acetyl-L-tryptophan, the serum level of deuterated tryptophan remained below 20% of total serum tryptophan, and serum protein fell below the normal range. It is concluded that the nutritive value of N-acetyl-L-tryptophan is inferior to that of L-tryptophan. Contradictory findings of earlier studies are discussed.     

Diagnosis and therapy of candidiasis in the premature infant

Extension of intensive care seems to have increased the risk of systemic candida infection. We report the incidence of systemic candida infection in 8 low-birth-weight infants (gestational age 27-32 weeks, birth weight 710-1,550 g). All infants required respiratory treatment. Various silastic catheters were inserted. Antibiotic therapy was started on the first day of life, usually a combination of ampicillin and gentamycin. Candida septicaemia was diagnosed at the age of 8-69 days of life based on blood and urine cultures, in two children at autopsy. There were no specific clinical symptoms in regard to candida infection. Sonographic technique revealed hydronephrosis in 3 infants due to candida mycelium. Antimycotic therapy included amphotericin B (dosage 0.44-1.0 mg/kg X day) and 5-fluorocytosine (80-100 mg/kg X day) as well as a monotherapy of 5-fluorocytosine (100-200 mg/kg X day). Four children were treated successfully. We like to advice a regular search for candida in urine, blood, tracheal secretion, stool and skin in low-birth-weight infants under intensive care conditions. If antimycotic therapy is started in time, therapy can be successful.     

Morton neuroma: sonographic evaluation

One hundred consecutive patients with symptoms suggestive of Morton neuroma were examined with sonography, and 134 intermetatarsal masses were demonstrated. Forty-five patients underwent surgical exploration, which revealed Morton neuromas. The typical sonographic appearance is that of an ovoid, hypoechoic mass oriented parallel to the long axis of the metatarsals. Most masses were between the second and third or third and fourth metatarsals and seemed to produce symptoms when reaching a diameter of 5 mm.     

Genetic counselling and the intention to undergo prophylactic mastectomy: effects of a breast cancer risk assessment

Scientific reports suggest that women at risk for familial breast cancer may benefit from prophylactic mastectomy. However, few data are available about how women decide upon this clinical option, and in particular, what role an objective risk assessment plays in this. The purpose of the present study is to assess whether this objective risk information provided in genetic counselling affects the intention for prophylactic mastectomy. Additionally, the (mediating) effects of breast cancer worry and perceived risk are investigated. A total of 241 women completed a questionnaire before and after receiving information about their familial lifetime breast cancer risk in a genetic counselling session. Path analysis showed that the objective risk information had a corrective effect on perceived risk (beta=0.38; P=0.0001), whereas the amount of breast cancer worry was not influenced by the counselling session. The objective risk information did not directly affect the intention for prophylactic mastectomy. The intention was influenced by perceived risk after counselling (beta=0.23; P=0.002), and by the precounselling levels of perceived risk (beta=0.27; P=0.00025) and breast cancer worry (beta=0.32; P=0.0001), that is, higher levels of perceived risk and breast cancer worry imply a stronger intention for prophylactic mastectomy. A personal history of breast cancer did not directly influence the intention for prophylactic mastectomy, but affected women who had undergone a mastectomy as surgical treatment were more positively inclined to have a prophylactic mastectomy than women who had had breast-conserving therapy. The impact of objective risk information on the intention for prophylactic mastectomy is limited and is mediated by perceived risk. Important determinants of the intention for prophylactic mastectomy were precounselling levels of breast cancer worry and perceived risk, suggesting that genetic counselling is only one event in the entire process of decision making. Therefore, interventions aimed at improving decision making on prophylactic mastectomy should explicitly address precounselling factors, such as personal beliefs and the psychological impact of the family medical history.